For a long time, medical imaging was mainly based on the physical principles of X-Ray Radiography and ultrasonography. The progress on these two techniques occurred mainly at the level of image detection, software for image processing and data storing. Recently, other techniques, based on different physical mechanisms, gave to the field of medical imaging new horizons on the exploration of human body's morphology and functionality.
A recent example is Positron Emission Tomography, PET, mainly used on cancer detection, with proved effective cost-benefit in cancer detection, staging and evaluation of therapy efficacy. The underlying principle of PET systems, as any other nuclear medicine method, is the detection of gamma radiation from a radioactive substance injected into the human body. In PET, the radioactive substance includes radioisotopes of atoms existing in biological molecules and so, with more affinity to certain biochemical mechanisms and cells (e.g. glucose-based FDG is fixed preferentially by cancerous cells, due to their higher metabolic rate). The molecule used as a label of the physiopathological process is marked with a positron emission, which after annihilation with an atomic electron emits two mono-energetic photons in opposite directions. A radiation detection system is needed to identify the presence and the spatial origin of the photons. Spatial origin of the photons is determined by the intersection of several lines generated by the emission of photons pairs.
1.1 Cancer Detection
The early detection of cancer is becoming a priority in healthcare policy of an increasing number of countries. Particularly important is the detection of breast cancer. A very large number of women (about one woman in nine) will develop a breast cancer, which is the second leading cause of cancer death in women of all ages, and the leading cause of death in those aged 40 to 49. [L. W. Basset, Jackson V. P, Diagnosis of Diseases of the Breast. W. B. Saunders Company. 1997. Chapter 23]. On the other hand, early detection leads to very high cure rate [P. A. Newcomb, P. M. Lantz, Breast cancer research and treatment, 28(2), pp 97-106 (1993)].
Unfortunately the performance of conventional X-ray mammography is unsatisfactory. X-ray mammography has an overall sensitivity, number of true positive over total positive, of about 80%, depending on the breast type. For fatty breasts a sensitivity of 95% can be achieved with a lower limit in the size of a detectable tumor of about 5 mm, while for dense breasts the sensitivity drops to 70% with a lower limit in size of 10 to 20 mm. The size of the detectable tumor is important since the prognosis of cancer is related to its size. On the other hand, its specificity, the number of true negative over total negative, is rather low, typically around 30%. A large number of unnecessary biopsies or even axillary's dissections are therefore performed which have a high cost for the society, not considering the psychological aspect on the women.
On the other hand PET metabolic techniques using 18F-fluoro-deoxy-glucose (FDG) have demonstrated an excellent sensitivity to malignant tissues (nearly 100%) due to the much higher glucose consumption of cancerous cells as compared to normal tissue. PET using FDG as a tracer of tumor glucose metabolic activity is a non-invasive imaging technology which probes tissue and organs function rather than structure [U.S. Pat. No. 5,453,623, U.S. Pat. No. 5,961,457].
This invention responds to the demand for a highly specific PET device having a spatial resolution of the order of 1 mm in order to efficiently detect stage 1a cancers.
1.2 Motivations for a Functional Imaging Device
Morphologic methods, like conventional X-Ray mammography or echography, provide images of the variations of the tissues density inside the body. The correlation between denser regions and cancer tumors is not always easy to establish, moreover cancer is very often characterized by low contrast structures in the domain of low energy X-rays, which leads to low sensitivity. This is particularly true for the 40% of women having dense breasts, for which X-rays mammography misses about 50% of cancers.
The high rate of false positive leads to a large number of unnecessary biopsies: 60 to 85% of the biopsies following an imaging indication, obtained with X-rays or ultrasounds, do not correspond to malign pathology [L. P. Adler, Beast Imaging Conference, Rome, May 2000]. An estimation of 600,000 unnecessary biopsies per year in the US only, correspond to a cost of 1 B$. More dramatic is the too large number of false negative with often fatal consequences for the patient. Other approaches, like MRI (Magnetic Resonance Imaging) and echography have not proven yet to be more efficient than X-rays.
There is clearly a need for much higher sensitivity and specificity. Moreover breast cancer not only needs diagnosis, but the biological rating is becoming increasingly useful. Tumor cells are known to metabolize glucose much faster than normal cells. Positron emission tomography (PET) using 18F-fluoro-deoxy-glucose (FDG) as a radiotracer is therefore likely to have a high sensitivity. Indeed a meta analysis study performed on 259 patients [L. P. Adler, Beast Imaging Conference, Rome, May 2000] has given sensitivity (true positive/total positive) of 92%, specificity (true negative number/total negative number) of 94%, and accuracy (true positive number+negative/total number) of 92%.
Although the clinical series are still limited, Positron Emission Tomography appears to be able to bring a significant improvement in the breast cancer diagnosis. The following results have been obtained using 18F-FDG:                a. In the diagnosis of malign neoplasms, sensitivities that vary between 77% [Yutani K et al. Detectability of FDG-PET and MIBI-SPECT to breast tumor, J Nucl Med. 1997; 38: 68P] and 100% [Yutani K et al. Correlation of F-18-FDG and Tc-99m-MIBI uptake with proliferative activity in breast cancer [abstract]. J Nucl Med. 1999; 40: 16-17P] and specificities between 84% [Avril N et al. Metabolic characterization of breast tumours with positron emission tomography with F-18 fluorodeoxyglucose. J Clin Oncol. 1996; 14: 1848-1857] and 100% [Noh D et al. Diagnostic value of positron emission tomography for detecting breast cancer. World J. Surg. 1998; 22: 223-228] were observed;        b. In what concerns the diagnosis of ganglion loco-regional invasion, fundamental for the initial staging of the disease, values of sensibility and accuracy of the order of 97 and 93%, respectively, have been measured [Bender H. et al. Breast imaging with positron emission tomography. In: Taillefer R, Khalkhali I, Waxman AD et al. Eds. Radionuclide imaging of the breast. New York: Marcel Dekker, 1998: 147-75].        
According to the experience with whole-body PET scanners, it seems that the sensitivity depends on lesion size: more than 90% for tumor sizes larger than 2 cm, but only around 25% for those smaller than 1 cm [Rosé C. et al. Nucl. Med. Commun. 2002; 23: 613-618]. These results may be significantly improved with the dedicated PET instrument proposed in this invention, specially the sensitivity to small tumors.
1.3 Motivations for a Partial-Body Camera Concept
Whole-body PET scanners are used clinically to diagnose and to stage a wide variety of cancers. Compared to whole body PET systems, dedicated partial-body equipment has potentially better spatial resolution, obtained with fine-grain crystal segmentation, and allows tighter coverage of the region under analysis, leading to a better sensitivity. Whole body PET system, because of their open geometry is also very sensitive to the background from the body, resulting in a lower target/background ratio. Moreover whole body PET systems are expensive and bulky.
Event counting sensitivity is an important parameter in PET, since when increased it allows a shorter examination time and lower injected dose, resulting on a lower radiation burden to the patient. Sensitivity depends on geometrical and physical parameters of the detector. The detector geometry should aim at solid angle coverage as large as possible, although some limitations are imposed by image reconstruction considerations as well as by the specifics of the human body anatomy and examination practice. The detector thickness and the crystal physical properties (density and composition) determine the photoelectric interaction probability for the emitted photons and in consequence have a direct impact on PET sensitivity.
On the other hand, the crystal length is responsible for the parallax effect in the image reconstruction process and the consequent degradation in position resolution. Parallax effect is an important issue especially when planar detectors located close to the object under examination are used. In consequence, we require high-density crystals combined with a method that provides depth of interaction information.
The ability to accumulate in a short time interval the event statistics needed for good image reconstruction depends on the performance of the data acquisition system. We require a data acquisition rate larger than 1 million events per second. This event rate corresponds, for example, to a total injected dose of 10 mCi, an uptake in the breast of 2% and a detector geometrical acceptance and efficiency as high as 10%. On the other hand, the detector will be subject to a large photon flux from decays occurring in the whole body. It is therefore important to reduce it as much as possible with a dedicated device, having a good acceptance for the organ under study, and a reduced acceptance for the rest of the body. Nevertheless is necessary that the data acquisition system to cope with a single photon background rate of the order of 10 MHz (2.5% of the total decays of 10 mCi dose). For these conditions, the combined efficiency of the readout electronics and data acquisition should be larger than 95%.
Under a large single photon background it is of paramount importance to achieve a very good time resolution to minimize accidental two-photon events. For the above-mentioned rates and for a photon time measurement r.m.s. of 1 ns, the background coincidence rate should be less than 30% of the true rate.
The number of events collected by unit time depends on the detector solid angle coverage. In the schematic layout where the ring diameter (Whole-body PET) or the separation between two plates (Partial-body PET) have a value D, the solid angle coverage varies with D−2. If we consider, as an example, that whole-body PET has a ring diameter of D=60 cm and the two plates separated by D=10 cm, the solid angle coverage of partial-body PET is about 15 times that of whole-body PET, assuming a factor 2.5 loss due to incomplete angular coverage of the dual-plate configuration.
The dual-plate system of this invention has a spatial resolution of 1-2 mm which is about 5 times better than typical whole-body PET systems. We conclude that the significance to small tumors (˜1-2 mm) in relation to whole-body PET is improved by a factor of the order of 10 due to better resolution and larger solid angle coverage.